DiaGenic ASA, Oslo, Norway.
J Parkinsons Dis. 2013;3(1):19-29. doi: 10.3233/JPD-120159.
A blood-based test for the early detection of Parkinson's disease (PD) would be an important diagnostic tool and useful for patient selection when developing novel drugs or treatments for the disease.
Here, we aimed to identify potential biomarkers associated with PD.
We applied gene expression profiling to the study of peripheral blood from 75 healthy control subjects and 79 PD patients at different stages of the disease. Healthy control subjects were matched for age and gender with PD subjects, and the diagnosis of patients was based on clinical evaluation by specialists in movement disorders. RNA was extracted from the blood samples and the gene expressions were measured using the Illumina HumanHT-12 v4.0 Expression BeadChip.
Our results support previous studies that gene expression in blood may be instrumental in the search for molecular biomarkers for PD. Single cross-validation results show that PD can be correctly classified from healthy controls with an agreement of 88% to clinical diagnosis. De novo PD patients are classified with a sensitivity of 87%, which is close to what was achieved for the patients having a confirmed PD diagnosis with disease duration <5 and >5 years (93% and 88%). A double cross-validation procedure showed that using a selected set of around 650 informative genes, similar results are achieved. Functional analysis of the selected genes showed genes significantly associated to mitochondrial dysfunction, protein ubiquitination, gene expression and cell death.
PD affects gene expression in blood, suggesting the potential for the development of a blood-based gene expression test.
一种用于帕金森病（PD）早期检测的血液检测方法将是一种重要的诊断工具，对于开发治疗该疾病的新型药物或疗法时的患者选择也非常有用。
本研究旨在寻找与 PD 相关的潜在生物标志物。
我们应用基因表达谱分析方法研究了 75 名健康对照者和 79 名处于不同疾病阶段的 PD 患者的外周血。健康对照者与 PD 患者在年龄和性别上相匹配，患者的诊断基于运动障碍专家的临床评估。从血液样本中提取 RNA，并使用 Illumina HumanHT-12 v4.0 Expression BeadChip 测量基因表达。
我们的结果支持了先前的研究，即血液中的基因表达可能有助于寻找 PD 的分子生物标志物。单交叉验证结果表明，PD 可以正确地从健康对照者中分类，其与临床诊断的一致性为 88%。新发 PD 患者的分类敏感性为 87%，这与病程<5 年和>5 年的确诊 PD 患者（93%和 88%）的分类结果接近。双重交叉验证程序表明，使用一组约 650 个有信息的基因，可以获得类似的结果。对选定基因的功能分析表明，与线粒体功能障碍、蛋白质泛素化、基因表达和细胞死亡显著相关的基因。
PD 影响血液中的基因表达，表明开发基于血液的基因表达测试具有潜力。
